Department of Anatomic Pathology, Faculty of Medicine Universitas Indonesia-Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia.
Asian Pac J Cancer Prev. 2024 May 1;25(5):1607-1613. doi: 10.31557/APJCP.2024.25.5.1607.
Response to neoadjuvant chemotherapy (NC) in individuals with invasive breast cancer (IBC) must be monitored, and biomarkers are needed. NC can activate an anti-tumour immune response in its microenvironment, known as Tumor-infiltrating Lymphocytes (TIL). TIL components believed to have great potential as predictors are CD4+, CD8+, and FOXP3+ TIL. This study aims to explore TIL components that can potentially be predictive biomarkers of NC pathological responses.
A sample size of 40 were analyzed based on the relationship between CD4+, CD8+, and FOXP3+ TIL expression with the Miller-Payne (MP) grading system. Age, tumour grade, PR, ER, Ki-67, and HER2 were also evaluated. CD4+, CD8+, and FOXP3+ TIL expressions were analayzed by IHC staining, while other data were collected from archives. Data was analyzed using univariate and multivariate analysis.
Univariate analysis showed a significant relationship between CD4+ TIL and MP (p<0.001), CD8+ and MP (p=0.004), and FOXP3 with MP (p<0.001). The simultaneous integration of the three biomarkers in one model was not good enough to be a predictive model. Therefore, an exploratory analysis was conducted by testing several alternative models that combined two of the three existing biomarkers. It turned out that CD4+ TIL in model 2 (CD4+CD8+) and FOXP3+ TIL in model 4 (CD8+FOXP3+) showed significant coefficient values. Moreover, all of the threshold coefficients in model 4 are significant.
This study shows that CD4+, CD8+, and FOXP3+ TIL have promising potential as predictive biomarkers. In particular, FOXP3+ is dominant in predictive models of pathological response in patients with IBC.
新辅助化疗（NC）治疗浸润性乳腺癌（IBC）的疗效必须进行监测，需要寻找生物标志物。NC 可在肿瘤微环境中激活抗肿瘤免疫应答，即肿瘤浸润淋巴细胞（TIL）。TIL 中的 CD4+、CD8+ 和 FOXP3+ 被认为具有成为预测标志物的巨大潜力。本研究旨在探讨 TIL 成分作为 NC 病理反应预测性生物标志物的潜在可能性。
根据 CD4+、CD8+ 和 FOXP3+ TIL 表达与 Miller-Payne（MP）分级系统之间的关系，分析了 40 例样本。还评估了年龄、肿瘤分级、PR、ER、Ki-67 和 HER2。通过免疫组化染色分析 CD4+、CD8+ 和 FOXP3+ TIL 的表达，其他数据则从档案中收集。采用单变量和多变量分析进行数据分析。
单变量分析显示，CD4+TIL 与 MP（p<0.001）、CD8+与 MP（p=0.004）和 FOXP3 与 MP 之间存在显著相关性（p<0.001）。将这三种生物标志物同时整合到一个模型中，不足以成为预测模型。因此，通过测试几种结合现有三种生物标志物中的两种的替代模型，进行了探索性分析。结果表明，模型 2（CD4+CD8+）中的 CD4+TIL 和模型 4（CD8+FOXP3+）中的 FOXP3+TIL 的系数值具有显著意义。此外，模型 4 中的所有阈值系数均具有显著意义。
本研究表明，CD4+、CD8+ 和 FOXP3+ TIL 具有成为预测生物标志物的巨大潜力。特别是在 IBC 患者病理反应预测模型中，FOXP3+ 占据主导地位。
